Details

Autor(en) / Beteiligte

• Jellusova, Julia
• Cato, Matthew H
• Apgar, John R
• Ramezani-Rad, Parham
• Leung, Charlotte R
• Chen, Cindi
• Richardson, Adam D
• Conner, Elaine M
• Benschop, Robert J
• Woodgett, James R
• Rickert, Robert C

Titel

Gsk3 is a metabolic checkpoint regulator in B cells

Ist Teil von

• Nature immunology, 2017-03, Vol.18 (3), p.303-312

Ort / Verlag

United States

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• B cells predominate in a quiescent state until an antigen is encountered, which results in rapid growth, proliferation and differentiation of the B cells. These distinct cell states are probably accompanied by differing metabolic needs, yet little is known about the metabolic control of B cell fate. Here we show that glycogen synthase kinase 3 (Gsk3) is a metabolic sensor that promotes the survival of naive recirculating B cells by restricting cell mass accumulation. In antigen-driven responses, Gsk3 was selectively required for regulation of B cell size, mitochondrial biogenesis, glycolysis and production of reactive oxygen species (ROS), in a manner mediated by the co-stimulatory receptor CD40. Gsk3 was required to prevent metabolic collapse and ROS-induced apoptosis after glucose became limiting, functioning in part by repressing growth dependent on the myelocytomatosis oncoprotein c-Myc. Notably, we found that Gsk3 was required for the generation and maintenance of germinal center B cells, which require high glycolytic activity to support growth and proliferation in a hypoxic microenvironment.